SARS1

seryl-tRNA synthetase 1, the group of Aminoacyl tRNA synthetases, Class II

Basic information

Region (hg38): 1:109213917-109238182

Previous symbols: [ "SARS" ]

Links

ENSG00000031698 ∙ NCBI:6301 ∙ OMIM:607529 ∙ HGNC:10537 ∙ Uniprot:P49591 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• autosomal recessive non-syndromic intellectual disability (Supportive), mode of inheritance: AR
• neurodevelopmental disorder with microcephaly, ataxia, and seizures (Moderate), mode of inheritance: AR
• neurodevelopmental disorder with microcephaly, ataxia, and seizures (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with microcephaly, ataxia, and seizures	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Musculoskeletal; Neurologic	28236339

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SARS1 gene.

• SARS1-related disorder (1 variants)
• not provided (1 variants)
• Cerebral arteriovenous malformation (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SARS1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	4	1	6
missense	1	1	15	2		19
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)	1					1
splice region				1	2	3
non coding					2	2
Total	2	1	16	6	3

Variants in SARS1

This is a list of pathogenic ClinVar variants found in the SARS1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-109214040-A-G		SARS1-related disorder	Likely benign (Apr 15, 2019)
1-109214083-G-A		not specified	Uncertain significance (Oct 27, 2022)
1-109214096-A-G		not specified	Uncertain significance (Nov 01, 2022)
1-109214118-G-A		See cases	Uncertain significance (Oct 06, 2021)
1-109228386-C-T		not specified	Uncertain significance (Jun 01, 2023)
1-109228424-G-A		not specified	Likely benign (Apr 14, 2022)
1-109228441-T-C		Neurodevelopmental disorder with microcephaly, ataxia, and seizures	Benign (Nov 07, 2021)
1-109229463-C-G		not specified	Uncertain significance (Dec 21, 2022)
1-109229480-G-A		not specified	Uncertain significance (Nov 06, 2023)
1-109229487-G-A		SARS1-related disorder	Uncertain significance (Oct 25, 2023)
1-109229572-G-A			Benign (Dec 31, 2019)
1-109230915-G-A		not specified	Uncertain significance (Aug 16, 2021)
1-109230944-G-A		Neurodevelopmental disorder with microcephaly, ataxia, and seizures	Pathogenic (Jul 01, 2022)
1-109231677-G-T		Neurodevelopmental disorder with microcephaly, ataxia, and seizures	Likely pathogenic (-)
1-109235318-C-T		not specified	Uncertain significance (Apr 07, 2022)
1-109235353-G-T		SARS1-related disorder	Likely benign (Dec 31, 2019)
1-109235366-C-T		Neurodevelopmental disorder with microcephaly, ataxia, and seizures	Pathogenic (Apr 19, 2023)
1-109235412-G-A		Neurodevelopmental disorder with microcephaly, ataxia, and seizures	Uncertain significance (Apr 27, 2019)
1-109235430-AGGT-A		SARS1-related disorder	Pathogenic (Apr 27, 2023)
1-109235955-T-C		Neurodevelopmental disorder with microcephaly, ataxia, and seizures	Benign (Nov 07, 2021)
1-109235978-T-C		Cerebral arteriovenous malformation	Pathogenic (Feb 14, 2018)
1-109236048-C-T			Likely benign (Jan 30, 2018)
1-109236451-G-A		Hyperuricemia, pulmonary hypertension, renal failure, alkalosis syndrome	Benign/Likely benign (May 01, 2024)
1-109236459-C-T		Neurodevelopmental disorder with microcephaly, ataxia, and seizures	Pathogenic (Apr 19, 2023)
1-109236487-C-T		Neurodevelopmental disorder with microcephaly, ataxia, and seizures • not specified	Uncertain significance (Apr 27, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SARS1	protein_coding	protein_coding	ENST00000234677	11	24252

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000749	125744	0	3	125747	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.66	170	299	0.568	0.0000170	3378
Missense in Polyphen		36	114.75	0.31372		1309
Synonymous	1.48	94	114	0.823	0.00000639	973
Loss of Function	4.70	2	29.6	0.0675	0.00000175	321

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000176	0.0000176
Middle Eastern	0.0000544	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Catalyzes the attachment of serine to tRNA(Ser) in a two-step reaction: serine is first activated by ATP to form Ser- AMP and then transferred to the acceptor end of tRNA(Ser) (PubMed:22353712, PubMed:24095058, PubMed:9431993, PubMed:26433229, PubMed:28236339). Is probably also able to aminoacylate tRNA(Sec) with serine, to form the misacylated tRNA L-seryl-tRNA(Sec), which will be further converted into selenocysteinyl-tRNA(Sec) (PubMed:9431993, PubMed:26433229, PubMed:28236339). In the nucleus, binds to the VEGFA core promoter and prevents MYC binding and transcriptional activation by MYC (PubMed:24940000). Recruits SIRT2 to the VEGFA promoter, promoting deacetylation of histone H4 at 'Lys-16' (H4K16). Thereby, inhibits the production of VEGFA and sprouting angiogenesis mediated by VEGFA (PubMed:19423848, PubMed:19423847, PubMed:24940000). {ECO:0000269|PubMed:19423847, ECO:0000269|PubMed:19423848, ECO:0000269|PubMed:22353712, ECO:0000269|PubMed:24095058, ECO:0000269|PubMed:24940000, ECO:0000269|PubMed:26433229, ECO:0000269|PubMed:28236339, ECO:0000269|PubMed:9431993}.
• Disease: DISEASE: Neurodevelopmental disorder with microcephaly, ataxia, and seizures (NEDMAS) [MIM:617709]: An autosomal recessive disorder characterized by delayed psychomotor development, intellectual disability, seizures apparent in infancy, impaired speech, and aggressive behavior. Additional features include microcephaly, ataxia, and muscle weakness. {ECO:0000269|PubMed:28236339}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Aminoacyl-tRNA biosynthesis - Homo sapiens (human);3-Phosphoglycerate dehydrogenase deficiency;Non Ketotic Hyperglycinemia;Glycine and Serine Metabolism;Dimethylglycine Dehydrogenase Deficiency;Hyperglycinemia, non-ketotic;Dimethylglycine Dehydrogenase Deficiency;Sarcosinemia;Dihydropyrimidine Dehydrogenase Deficiency (DHPD);tRNA Aminoacylation;Translation;Selenocysteine synthesis;Metabolism of proteins;Metabolism of amino acids and derivatives;Glycine Serine metabolism;selenocysteine biosynthesis;Metabolism;tRNA charging;Selenoamino acid metabolism;Cytosolic tRNA aminoacylation (Consensus)

Recessive Scores

• pRec: 0.261

Intolerance Scores

• loftool: 0.145
• rvis_EVS: -0.32
• rvis_percentile_EVS: 31.69

Haploinsufficiency Scores

• pHI: 0.190
• hipred: Y
• hipred_score: 0.749
• ghis: 0.547

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.999

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Sars

Zebrafish Information Network

• Gene name: sars
• Affected structure: trunk vasculature
• Phenotype tag: abnormal
• Phenotype quality: branchiness

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;translation;tRNA aminoacylation for protein translation;seryl-tRNA aminoacylation;tRNA processing;selenocysteine metabolic process;negative regulation of angiogenesis;selenocysteinyl-tRNA(Sec) biosynthetic process;negative regulation of vascular endothelial growth factor production
• Cellular component: nucleus;cytoplasm;cytosol;extracellular exosome
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;RNA binding;serine-tRNA ligase activity;protein binding;ATP binding;protein homodimerization activity;selenocysteine-tRNA ligase activity